A Study to Evaluate the Safety of Nivolumab and Ipilimumab in Subjects With Previously Untreated Advanced or Metastatic Renal Cell Cancer

Renal Cell Carcinoma Clinical Trial

— CHECKMATE 920  

Official title:

Phase 3b/4 Safety Trial of Nivolumab Combined With Ipilimumab in Subjects With Previously Untreated, Advanced or Metastatic RCC (CheckMate 920: CHECKpoint Pathway and nivoluMAb Clinical Trial Evaluation 920)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02982954
• Other study ID #: CA209-920
• Status: Completed
• Phase: Phase 4
• Start date: January 16, 2017
• Est. completion date: October 6, 2021

Study information

• Verified date: October 2022
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To investigate the safety of Nivolumab in combination with Ipilimumab in subjects with previously untreated advanced or metastatic Renal Cell Cancer.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 211
• Est. completion date: October 6, 2021
• Est. primary completion date: May 11, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Type of Participant and Target Disease Characteristics

1. Advanced or metastatic RCC

2. Histologically confirmed, previously untreated (treatment-naive) RCC

3. No prior systemic therapy for RCC except for one prior adjuvant or neoadjuvant therapy for completely resectable RCC

4. Measurable disease as per RECIST 1.1. Subject must have extracranial metastasis as measurable disease

5. Karnofsky Performance Status (KPS) of at least 70% for Cohort 1, 2, and 3; KPS of 50-60% for Cohort 4

6. Tumor tissue need be received by the central vendor (block or unstained slides). Note:

Fine Needle Aspiration (FNA)and bone metastases samples are not acceptable for submission.

Exclusion Criteria:

1. Medical Conditions

1. Subjects with any active autoimmune disease or a history of known autoimmune disease

2. Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured

3. Known HIV or AIDS-related illness

4. Any positive test for hepatitis B or hepatitis C virus indicating acute or chronic infection.

2. Prior/Concomitant Therapy

1. Prior systemic treatment in the metastatic setting with Vascular epithelial growth factor(VEGF) or VEGF receptor targeted therapy

2. Prior treatment with an anti-Programmed Death (PD) -1, anti-PD-L1, anti-PD-L2, anti-cluster of differentiation 137 (CD137), or anti-cytotoxic T-lymphocyte-associated antigen 4(CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways. This includes the utilization of these agents in the neo-adjuvant or adjuvant setting.

3. Anti-cancer therapy less than 28 days prior to the first dose of study drug or palliative, focal radiation therapy less than 14 days prior to the first dose of study drug.

Other protocol defined inclusion/exclusion criteria apply

Related Conditions & MeSH terms

• Carcinoma, Renal Cell
• Renal Cell Carcinoma

Intervention

Drug:
• Nivolumab
Specified dose on specified day
• Ipilimumab
Specified Dose on Specified Day

Locations

Country	Name	City	State
United States	University Of New Mexico	Albuquerque	New Mexico
United States	Alaska Urological Institute dba Alaska Clinical Research Center	Anchorage	Alaska
United States	Emory University - Winship Cancer Institute	Atlanta	Georgia
United States	Texas Oncology	Austin	Texas
United States	Montefiore Medical Center	Bronx	New York
United States	Maimonides Medical Center	Brooklyn	New York
United States	Southdale Cancer Clinic	Burnsville	Minnesota
United States	Ironwood Cancer And Research Centers, Pc	Chandler	Arizona
United States	Charleston Hematology Oncology Associates, Pa	Charleston	South Carolina
United States	Hollings Cancer Center	Charleston	South Carolina
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Tennessee Oncology, PLLC - SCRI - PPDS	Chattanooga	Tennessee
United States	Local Institution - 0009	Coon Rapids	Minnesota
United States	Texas Oncology	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	eCare	Encinitas	California
United States	Local Institution - 0042	Fairfax	Virginia
United States	Local Institution - 0028	Fayetteville	Arkansas
United States	Florida Cancer Specialists S.	Fort Myers	Florida
United States	Local Institution - 0012	Fort Wayne	Indiana
United States	Texas Oncology-Fort Worth 12th Ave	Fort Worth	Texas
United States	Southeastern Medical Oncology Center	Goldsboro	North Carolina
United States	St. Francis Cancer Treatment Center	Grand Island	New York
United States	Local Institution - 0023	Hackensack	New Jersey
United States	Hattiesburg Clinic	Hattiesburg	Mississippi
United States	Jackson Oncology Associates, Pllc	Jackson	Mississippi
United States	Broome Oncology	Johnson City	New York
United States	HCA Midwest Division	Kansas City	Missouri
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Pacific Shores Medical Group	Long Beach	California
United States	Los Angeles Cancer Network	Los Angeles	California
United States	UCLA Hematology Oncology	Los Angeles	California
United States	Norton Cancer Institute	Louisville	Kentucky
United States	University of Wisconsin Clinical Science Center	Madison	Wisconsin
United States	University Of Miami/Sylvester Cancer Center	Miami	Florida
United States	Texas Oncology-Midland Allison Cancer Center	Midland	Texas
United States	Bon Secours St Francis Hospital	Midlothian	Virginia
United States	Park Nicollet Clinic Cancer Center	Minneapolis	Minnesota
United States	Northwest Alabama Cancer Center, Pc	Muscle Shoals	Alabama
United States	Local Institution - 0002	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Local Institution - 0052	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Illinois Cancer Specialists	Niles	Illinois
United States	UF Health Cancer Center at Orlando Health	Orlando	Florida
United States	Local Institution - 0071	Pittsburgh	Pennsylvania
United States	Torrance Health Association	Redondo Beach	California
United States	Virginia Cancer Institute	Richmond	Virginia
United States	Kaiser Permanente Medical Group - Southern California	Riverside	California
United States	Florida Cancer Specialists	Saint Petersburg	Florida
United States	Texas Oncology	San Antonio	Texas
United States	Sharp Memorial Hospital	San Diego	California
United States	Coastal Integrative Cancer Care	San Luis Obispo	California
United States	Central Coast Med Oncology	Santa Maria	California
United States	University of Washington - Seattle Cancer Care Alliance	Seattle	Washington
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Medical Oncology Associates	Spokane	Washington
United States	SUNY Upstate Medical University	Syracuse	New York
United States	Oklahoma Cancer Specialists and Research Institute, LLC-Clinical Research	Tulsa	Oklahoma
United States	Cancer Center Of Kansas	Wichita	Kansas
United States	Yakima Valley Memorial Hospital/North Star Lodge	Yakima	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With High Grade (Grade 3-4) Immune Mediated Adverse Events (IMAEs)	Number of participants with IMAEs in the following categories: Skin, Endocrine, Gastrointestinal, Hepatic, Renal, Pulmonary and Hypersensitivity	Approximately 39 Months
Primary	Number of Participants With High Grade (Grade 5) Immune Mediated Adverse Events (IMAEs)	Number of participants with IMAEs in the following categories: Skin, Endocrine, Gastrointestinal, Hepatic, Renal, Pulmonary and Hypersensitivity	Approximately 39 Months
Secondary	Time to Onset of Grade 3-5 Immune Mediated Adverse Events (IMAEs)	Time to onset is defined as the duration of time in weeks from the first dosing to the immune modulating adverse event onset date. Participants experiencing all high grade (CTCAE v4 Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) in the following categories will be included: Skin, Endocrine, Gastrointestinal, Hepatic, Renal, Pulmonary and Hypersensitivity. IMAEs are specific events (or groups of preferred terms describing specific events) considered as potential immune-mediated events by investigator, that meet the following definition: (1) those occurring within 100 days of the last dose (2) regardless of causality (3) with no clear alternate etiology based on investigator assessment, or with an immune-mediated component and (4) treated with immune-modulating medication. Grade 3= Severe reaction, Grade 4 = Life-threatening, Grade 5 = Death	From first dose to the earliest IMAE (grade 3-5) event onset date (up to approximately 116 weeks)
Secondary	Time to Resolution of Grade 3-5 Immune Mediated Adverse Events (IMAEs)	Time to resolution is defined as the longest time from IMAE onset date to complete resolution or improvement to the grade at baseline experienced by the participant (the IMAE end date). Participants experiencing all high grade (CTCAE v4 Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) in the following categories will be included: Skin, Endocrine, Gastrointestinal, Hepatic, Renal, Pulmonary and Hypersensitivity. IMAEs are specific events (or groups of preferred terms describing specific events) considered as potential immune-mediated events by investigator, that meet the following definition: (1) those occurring within 100 days of the last dose (2) regardless of causality (3) with no clear alternate etiology based on investigator assessment, or with an immune-mediated component and (4) treated with immune-modulating medication. Grade 3= Severe reaction, Grade 4 = Life-threatening, Grade 5 = Death	From the IMAE onset date to the IMAE end date, up to approximately 194 weeks
Secondary	Number of Participants Who Received Immune Modulating Medication for High Grade (Grades 3-5) Immune Mediated Adverse Events (IMAEs)	The number of participants who received immune modulating medication for participants experiencing all high grade (CTCAE v4 Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) in the following categories will be included: Skin, Endocrine, Gastrointestinal, Hepatic, Renal, Pulmonary and Hypersensitivity. IMAEs are specific events (or groups of preferred terms describing specific events) considered as potential immune-mediated events by investigator, that meet the following definition: (1) those occurring within 100 days of the last dose (2) regardless of causality (3) with no clear alternate etiology based on investigator assessment, or with an immune-mediated component and (4) treated with immune-modulating medication. Grade 3= Severe reaction, Grade 4 = Life-threatening, Grade 5 = Death	From first dose up to 100 days post last dose (up to approximately 29 months)
Secondary	Number of Participants Who Received Hormone Replacement Therapy for High Grade (Grades 3-5) Immune Mediated Adverse Events (IMAEs)	The number of participants who received Hormone Replacement Therapy for experiencing all high grade (CTCAE v4 Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) in the following categories will be included: Skin, Endocrine, Gastrointestinal, Hepatic, Renal, Pulmonary and Hypersensitivity. IMAEs are specific events (or groups of preferred terms describing specific events) considered as potential immune-mediated events by investigator, that meet the following definition: (1) those occurring within 100 days of the last dose (2) regardless of causality (3) with no clear alternate etiology based on investigator assessment, or with an immune-mediated component and (4) treated with immune-modulating medication. Grade 3= Severe reaction, Grade 4 = Life-threatening, Grade 5 = Death	From first dose up to 100 days post last dose (up to approximately 29 months)
Secondary	Number of Participants Who Received = 40mg of Prednisone for High Grade (Grades 3-5) Immune Mediated Adverse Events (IMAEs)	The number of participants who received = 40mg of prednisone for high grade (grades 3-5) IMAEs. Participants experiencing all high grade (CTCAE v4 Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) in the following categories will be included: Skin, Endocrine, Gastrointestinal, Hepatic, Renal, Pulmonary and Hypersensitivity. IMAEs are specific events (or groups of preferred terms describing specific events) considered as potential immune-mediated events by investigator, that meet the following definition: (1) those occurring within 100 days of the last dose (2) regardless of causality (3) with no clear alternate etiology based on investigator assessment, or with an immune-mediated component and (4) treated with immune-modulating medication. Grade 3= Severe reaction, Grade 4 = Life-threatening, Grade 5 = Death	From first dose up to 100 days post last dose (up to approximately 29 months)
Secondary	Median Progression Free Survival (PFS)	PFS is defined as the time from first dose to the date of the first documented progressive disease (PD) as determined by the investigator (per RECIST 1.1 criteria or clinical) or death due to any cause whichever occur first. Progressive disease is defined as progression of existing non-target lesions or at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.	From first dose to the date of the first documented progressive disease, up to approximately 12 months
Secondary	Objective Response Rate (ORR)	ORR is defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of response evaluable participants. Best overall response is defined as the best response recorded from the start of the study treatment until the end of treatment. The participant's best overall response assignment will depend on the findings of both target and non-target disease and will also take into consideration the appearance of new lesions. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all lesions and normalization of tumor marker level. All lymph nodes (whether target or non-target) must be non-pathological in size (< 10mm short axis).	From first dose up to the date of objectively documented progression or the date of subsequent therapy, whichever occurs first (up to approximately 26 months)
Secondary	Time to Response Rate (TRR)	TTR is defined as the median percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of response evaluable participants. Best overall response is defined as the best response recorded from the start of the study treatment until the end of treatment. The participant's best overall response assignment will depend on the findings of both target and non-target disease and will also take into consideration the appearance of new lesions. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all lesions and normalization of tumor marker level. All lymph nodes (whether target or non-target) must be non-pathological in size (< 10mm short axis).	From the date of first dose to first documented CR or PR, up to approximately 15 months
Secondary	Duration of Response (DOR)	DOR is defined as the time between the date of first confirmed response to the date of the first documented tumor progression per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, or death due to any cause, whichever occurs first. DOR will be computed for participants who achieve partial response (PR) or complete response (CR) only. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all lesions and normalization of tumor marker level. All lymph nodes (whether target or non-target) must be non-pathological in size (< 10mm short axis).	From first confirmed response to the date of the first documented tumor progression or death, up to approximately 48 months

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting
•   FDA Safety Alerts and Recalls